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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04638153




Registration number
NCT04638153
Ethics application status
Date submitted
15/09/2020
Date registered
20/11/2020
Date last updated
15/02/2024

Titles & IDs
Public title
A Study Of Safety, Tolerability And Effectiveness Of Recifercept In Children With Achondroplasia
Scientific title
A PHASE 2 MULTIPLE DOSE, RANDOMIZED STUDY TO ASSESS THE SAFETY, TOLERABILITY, PHARMACOKINETICS AND EFFICACY OF RECIFERCEPT IN CHILDREN WITH ACHONDROPLASIA
Secondary ID [1] 0 0
2020-001189-13
Secondary ID [2] 0 0
C4181005
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Recifercept

Experimental: Low Dose - Low Dose

Experimental: Medium Dose - Medium Dose

Experimental: High Dose - High Dose

Experimental: PK Phase 2 Formulation - Phase 2 formulation [process 1c] 3mg/kg

Experimental: PK Phase 3 Formulation - Phase 3 formulation [process 2] 3mg/kg


Other interventions: Recifercept
Recifercept
Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs)
Timepoint [1] 0 0
The first dose up to 28 to 35 days after the last dose of study intervention (13 months)
Primary outcome [2] 0 0
Least Square Mean of Change From Baseline Height Growth at Month 3, Month 6, Month 9, and Month 12
Timepoint [2] 0 0
Baseline, Month 3, Month 6, Month 9, and Month 12
Secondary outcome [1] 0 0
Change From Baseline in Pulse Rate at Month 3, Month 6, Month 9, and Month 12
Timepoint [1] 0 0
Baseline, Month 3, Month 6, Month 9, and Month 12
Secondary outcome [2] 0 0
Change From Baseline in Respiratory Rate at Month 3, Month 6, Month 9, and Month 12
Timepoint [2] 0 0
Baseline, Month 3, Month 6, Month 9, and Month 12
Secondary outcome [3] 0 0
Change From Baseline in Blood Pressure at Month 3, Month 6, Month 9, and Month 12
Timepoint [3] 0 0
Baseline, Month 3, Month 6, Month 9, and Month 12
Secondary outcome [4] 0 0
Change From Baseline in Temperature at Month 3, Month 6, Month 9, and Month 12
Timepoint [4] 0 0
Baseline, Month 3, Month 6, Month 9, and Month 12
Secondary outcome [5] 0 0
Number of Participants With Abnormal Physical Examination Findings at Month 3, Month 6, Month 9, and Month 12
Timepoint [5] 0 0
Month 3, Month 6, Month 9, and Month 12
Secondary outcome [6] 0 0
Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)
Timepoint [6] 0 0
Baseline to Month 12
Secondary outcome [7] 0 0
Pre-Dose Serum Concentration (Ctrough) of Recifercept
Timepoint [7] 0 0
Pre-dose on Day(s) 4, 8, 15, 29, 61, 91, 183, 273, 365
Secondary outcome [8] 0 0
Number of Participants With Positive Anti-Drug Antibodies (ADA) and Neutralizing Antibody (NAb) of Recifercept
Timepoint [8] 0 0
The first dose up to 28 to 35 days after the last dose of study intervention (13 months)
Secondary outcome [9] 0 0
Change From Baseline in Sitting/Standing Height Ratio at Month 3, Month 6, Month 9, and Month 12
Timepoint [9] 0 0
Baseline, Month 3, Month 6, Month 9, and Month 12
Secondary outcome [10] 0 0
Least Square Mean of Change From Baseline Arm Span to Standing Height/Length Difference at Month 3, Month 6, Month 9, and Month 12
Timepoint [10] 0 0
Baseline, Month 3, Month 6, Month 9, and Month 12
Secondary outcome [11] 0 0
Change From Baseline in Knee Height : Lower Segment Ratio at Month 3, Month 6, Month 9, and Month 12
Timepoint [11] 0 0
Baseline, Month 3, Month 6, Month 9, and Month 12
Secondary outcome [12] 0 0
Change From Baseline in Occipito-Frontal Circumference at Month 3, Month 6, Month 9, and Month 12
Timepoint [12] 0 0
Baseline, Month 3, Month 6, Month 9, and Month 12
Secondary outcome [13] 0 0
Change From Baseline in Occipito-Frontal to Occipito-Mid-Face Ratio at Month 3, Month 6, Month 9, and Month 12
Timepoint [13] 0 0
Baseline, Month 3, Month 6, Month 9, and Month 12
Secondary outcome [14] 0 0
Change From Baseline in Height Standard Deviation Score (Z-Score) at Month 3, Month 6, Month 9, and Month 12
Timepoint [14] 0 0
Baseline, Month 3, Month 6, Month 9, and Month 12
Secondary outcome [15] 0 0
Change From Baseline in Fixed Flexion Angles at Elbow at Month 3, Month 6, Month 9, and Month 12
Timepoint [15] 0 0
Baseline, Month 3, Month 6, Month 9, and Month 12
Secondary outcome [16] 0 0
Change From Baseline in Body Mass Index (BMI) at Month 3, Month 6, Month 9, and Month 12
Timepoint [16] 0 0
Baseline, Month 3, Month 6, Month 9, and Month 12
Secondary outcome [17] 0 0
Change From Baseline in Waist : Chest Circumference Ratio at Month 9 and Month 12
Timepoint [17] 0 0
Baseline, Month 9, and Month 12
Secondary outcome [18] 0 0
Change From Baseline in Apnea-Hypopnea Index (AHI) at Month 12
Timepoint [18] 0 0
Baseline and Month 12
Secondary outcome [19] 0 0
Change From Baseline in Desaturation Index at Month 12
Timepoint [19] 0 0
Baseline and Month 12
Secondary outcome [20] 0 0
Change From Baseline in Polysomnography Other Parameters at Month 12
Timepoint [20] 0 0
Baseline and Month 12
Secondary outcome [21] 0 0
Change From Baseline in SaO2 Nadir at Month 12
Timepoint [21] 0 0
Baseline and Month 12

Eligibility
Key inclusion criteria
* Main cohort: Aged =2 years to <11 years (up to the day before 11th birthday inclusive) at time of enrollment; or exploratory cohort: aged =3 months to <2 years (up to the day before 2nd birthday inclusive) at time of enrollment
* Documented, confirmed genetic diagnosis of achondroplasia from historical medical records prior to entry into this trial (test must have been performed at a laboratory fully accredited for genetic testing under local regulations).
* Completed the C4181001 natural history study with at least 2 valid height/length measurements (at least 3 months apart) prior to enrollment in this study. One of these measurement timepoints must be within the 3 months prior to enrollment in C4181005.
* Tanner stage 1 based on investigator assessment during physical examination (must include assessment of breast development for females, testicular stage for males).
* Able to stand independently for height measurements (if =2 years of age at enrollment).
* If aged <2 years at enrollment, has a documented historical MRI brain/cervical spine performed in the previous 12 months.
Minimum age
3 Months
Maximum age
10 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Presence of co-morbid conditions or circumstances that, in the opinion of the investigator, would affect interpretation of growth data or ability to complete the trial procedures.
* Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
* Presence of severe obesity (BMI >95th percentile on Hoover-Fong BMI charts) [Hoover-Fong et al, 2008].14
* Known closure of long bone growth plates (cessation of height growth).
* Body weight <7 kg or >30 kg.
* Moderate or severe renal impairment CrCL GFR <60 mL/min/1.73m2 (Calculated GFR based on updated "bedside" Schwartz formula for pediatric patients (CrCL (mL/min/1.73 m2) = 0.413 * Height (cms)/ Serum cr (mg/dL) or hepatic impairment (AST/ALT >1.5 ULN).
* History of hypersensitivity to study intervention or any excipients.
* History of any prior treatment with human growth hormone or related products (including insulin-like growth factor 1 [IGF-1]).
* History of receipt of any treatment that are known to potentially affect growth (including oral steroids >5 days in the last 6 months, high dose inhaled corticosteroids (>800 mcg/day beclametasone equivalent) and medication for attention deficit hyperactivity disorder).
* History of limb lengthening surgery (defined as distraction osteogenesis/Ilizarov/callostasis technique following submetaphyseal osteotomy to extend bone length).
* Any limb lengthening/corrective orthopaedic surgery planned at any point during the trial period.
* Less than 6 months since fracture or surgical procedure of any bone determined from the screening visit date.
* Presence of any internal guided growth plates/devices.
* History of removal of internal guided growth plates/devices within less than 6 months.
* History of receipt of any investigational product for achondroplasia or that may affect growth/interpretation of growth parameters.
* History of receipt of an investigational product (not for achondroplasia/growth affecting) within the last 30 days or 5 half-lives (whichever is longer).

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
2/12/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
27/03/2023
Sample size
Target
Accrual to date
Final
60
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Murdoch Children's Research Institute - Melbourne
Recruitment hospital [2] 0 0
Murdoch Children's Research Institute - Parkville
Recruitment postcode(s) [1] 0 0
3052 - Melbourne
Recruitment postcode(s) [2] 0 0
3052 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Delaware
Country [3] 0 0
United States of America
State/province [3] 0 0
Texas
Country [4] 0 0
Belgium
State/province [4] 0 0
Edegem
Country [5] 0 0
Belgium
State/province [5] 0 0
Leuven
Country [6] 0 0
Denmark
State/province [6] 0 0
Copenhagen NV
Country [7] 0 0
Italy
State/province [7] 0 0
Roma
Country [8] 0 0
Japan
State/province [8] 0 0
Osaka
Country [9] 0 0
Japan
State/province [9] 0 0
Okayama
Country [10] 0 0
Portugal
State/province [10] 0 0
Coimbra
Country [11] 0 0
Spain
State/province [11] 0 0
Alava

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Pfizer
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Approximately 63 participants will be randomized to one of three doses to receive Recifercept either

* Low Dose
* Medium Dose
* High Dose

Participants will will attend the clinic at baseline and at Day 1, 4, 8, 15, 29 \& then Month 2, 3 6, 9 \& 12. Assessments include safety, blood sampling, physical examination, vital signs, anthropometric body measurements \& patient/caregiver quality of life questionnaires

Participants will received treatment with Recifercept for 12 months. All participants who complete the study and in the opinion of the investigator, continue to have a positive risk:benefit profile, will be offered to enroll into an open-label extension (OLE) study.

A PK cohort will include 12 participants who will randomly receive a single dose of 3 mg/kg of Phase 2 study (process 1c) formulation and a single dose of 3 mg/kg of the proposed Phase 3 (process 2) study formulation in a cross over study. Dose of the cohort could be changed due to emerging safety and efficacy data in the study.
Trial website
https://clinicaltrials.gov/study/NCT04638153
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Pfizer CT.gov Call Center
Address 0 0
Pfizer
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT04638153